A research team led by Professor Chang Zhijie at the School of Basic Medical Sciences, Tsinghua University, has published a pioneering clinical study on the use of inhaled human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-EVs) to treat pulmonary fibrosis. The paper, titled “Clinical investigation on nebulized human umbilical cord MSC-derived extracellular vesicles for pulmonary fibrosis treatment,” appears in the prestigious journal Signal Transduction and Targeted Therapy. 

Pulmonary fibrosis is a progressive and often fatal lung disease characterized by scarring of lung tissue. Current treatments remain limited in efficacy, and the prognosis is generally poor. As a result, developing safe and effective new therapies has become a pressing research priority. Among the most promising emerging strategies are stem cell-derived extracellular vesicles (EVs), though their clinical application remains in early stages.

In this study, Prof Chang’s team established a rigorous, standardized system for producing and characterizing hUCMSC-EVs, analyzing their miRNA, protein, and metabolite content. In animal models of bleomycin-induced pulmonary fibrosis, nebulized EVs targeted lung tissue effectively, significantly improving survival (from 20% to 80%), reducing lung damage, and restoring lung function and oxygen saturation.

Building on these preclinical findings, the team launched a randomized, single-blind, placebo-controlled Phase I clinical trial (Registration No. MR-46-22-004531; ChiCTR2300075466) with 24 participants. The results demonstrated good safety and tolerability of nebulized EV therapy, with no serious adverse events reported. Compared with standard care alone, patients who received inhaled EVs showed notable improvements in lung function (FVC, MVV) and respiratory health status, as assessed by the St. George’s Respiratory Questionnaire and Leicester Cough Questionnaire. Strikingly, imaging revealed significant resolution of lung lesions in two patients with post-inflammatory pulmonary fibrosis—suggesting potential for disease reversal.

“This study provides early but important clinical evidence supporting the safety and efficacy of EV-based inhalation therapy for pulmonary fibrosis,” said Prof Chang. “It lays a critical scientific foundation for future translation of cell-free therapies in respiratory medicine.”

The research also marks a significant step toward developing a standardized and scalable clinical pathway for EV-based therapeutics. It offers a non-invasive, immunologically safe approach that delivers active biologics directly to the alveoli—providing a novel option for conditions such as idiopathic pulmonary fibrosis (IPF), chronic interstitial lung diseases, and COPD-related fibrosis.

This work represents a collaborative effort among several leading institutions. Prof. Lu Xu (First Affiliated Hospital of Hainan Medical University) and Prof. Muyang Yan (PLA General Hospital) served as co-corresponding authors alongside Prof. Chang. Dr. Meng Li and Prof. Huaping Huang were co-first authors. Contributions also came from Prof. Xinbao Hao, Prof. Jun Li, Prof. Tongbiao Zhao, and Prof. Jianqiu Sheng, with additional support from Prof. Hang Yin, Prof. Zeping Hu, Dr. Gaoge Sun, and Dr. Ke Yao.

The study was supported by the Tsinghua Spring Breeze Fund, the Tsinghua-Vanke Public Health Development Fund, the Tsinghua–Shanghai Jinwei Cell Storage Joint Fund, the JinFeng Lab Project (Chongqing), and multiple funding agencies from Hainan Province.

As a next step, the research team plans to launch larger, multi-center clinical trials and deepen mechanistic investigations to fully realize the therapeutic potential of hUCMSC-EVs for pulmonary fibrosis and other respiratory diseases.